Cognitive effects of cancer better understood

By Susan Wood, PhD Mar 14, 2017

Treatment for cancer may include surgery, chemotherapy, radiation therapy, hormone therapy or a combination. Each treatment has the potential to lead to different effects on cognition.


Considerations for the surgical resection of brain tumors involve tumor location. Potential cognitive side effects are dependent on what areas of the brain are resected/disturbed by the procedure. Also, if an infection develops as a result of the surgery in the brain, cognition can be seriously affected.


For years, oncologists did not believe that chemotherapy could affect cognitive functioning. Chemotherapy molecules were thought to be too large to cross the ‘blood-brain barrier’ that protects the brain from fluctuations in plasma composition. However, patients were reporting deficits in cognition during and after treatment.

A landmark study changed how clinical practice was guided in this area. The first prospective, randomized, longitudinal study providing solid evidence of chemotherapy-related cognitive dysfunction was performed at the University of Texas MD Anderson Cancer Center in Houston. Through baseline and one-year post-therapy neuropsychological assessments, 61 percent of participants — women with non-metastatic breast cancer — were found to have an association between cognitive dysfunction and chemotherapy. Of this subset, 45 percent remained impaired after one year in the areas of: domains of attention, processing speed, and learning and memory. Also of note, a third of patients showed cognitive dysfunction prior to treatment, indicating that the disease itself contributes to dysfunction prior to receiving potentially neurotoxic therapies.

There now have been many studies providing a great deal of additional information. What was formerly called “chemobrain” has a new name: cancer-related cognitive impairment (CRCI). Mild impairment in areas consistent with dysfunction of the frontal and subcortical networks define CRCI, including:

  • Attention
  • Fine motor function
  • Information-processing speed
  • Learning and memory retrieval
  • Organization and multi-tasking

Today, approximately 40 percent of cancer patients have CRCI before treatment, up to 75 percent may have cognitive decline during treatment and up to 60 percent exhibit deterioration in cognition after completion of treatment. CRCI affects the occupational and social aspects of patients’ lives. It usually manifests following the initiation of chemotherapy treatment and up to a year after treatment is completed, with some patients experiencing persistent impairment.

Radiation therapy

Radiation therapy uses high-energy radiation to kill cancer cells by damaging their DNA. Treatment must be planned carefully to minimize side effects because normal cells, as well as cancer cells, can be damaged during radiation therapy. Through intensity-modulated radiation therapy (IMRT), a radiation oncologist chooses the radiation doses given to different areas of the tumor and surrounding tissue. A high-powered computer program then calculates the number of beams required, as well as the angles of the radiation treatment.

MD Anderson Cancer Center in Houston has pioneered proton beam treatment. Proton beams differ from photon beams mainly in the way they deposit energy in living tissue. Photons deposit energy in small packets, all along their path in the tissue. Protons, however, deposit much of their energy at the end of their path — the Bragg peak — depositing less energy along the way.

Stereotactic radiosurgery, or gamma knife, delivers a large, precise dose of radiation to the tumor area in a single session via radiosurgery, or in multiple sessions via radiotherapy, a treatment without actual surgery. It may be used for some tumors in parts of the brain or spinal cord that cannot be treated with surgery or when a patient is not healthy enough for surgery.

Complications of radiation therapy occur in stages:

  • Acute encephalopathy may develop within two weeks. It is characterized by headaches, drowsiness and worsening of pre-existing neurologic deficits.
  • Early effects may develop one to six months after radiotherapy treatment. They are associated with reversible damage to the protective covering surrounding the brain’s nerve fibers, related to disruption of the blood-brain barrier. Return to baseline is typically seen in one year.
  • Late effects may develop more than a year after radiotherapy treatment and are usually not reversible. These effects consist of local necrosis of brain tissue, and are associated with mild to severe cognitive deficits.
  • Whole brain irradiation often associated with metastatic disease generally results in more severe cognitive dysfunction.

Because radiation therapy can impair the growth of normal tissue and subsequent brain development, it is generally avoided in children under the age of 3.

Hormonal therapy

Hormone, or endocrine, therapies slow or stop the growth of hormone receptor-positive tumors by preventing cancer cells from getting the hormones they need to grow. The therapy is widely prescribed for patients with hormone-sensitive breast cancer, contributing to improved survival rates in a number of ways. Hormone therapies such as the drug tamoxifen attach to the receptor in the cancer cell, blocking estrogen from attaching to the receptor. Hormone therapies like aromatase inhibitors lower the level of estrogen in the body, starving cancer cells of the estrogen they need to grow. Both of these examples of hormone therapies lower the risk of breast cancer recurrence and breast cancer development in the opposite breast, as well as death from breast cancer.

A comparison study of hormonal treatments contrasted the effects of tamoxifen and the aromatase inhibitor exemestane on the cognitive functioning of post-menopausal patients with breast cancer. The study found after one year of therapy, tamoxifen was associated with lower functioning in verbal memory and executive function whereas exemestane was not.
In other studies, tamoxifen has been associated with significantly reduced performances on measures of memory, verbal fluency, visuospatial functioning and processing speed.

Assessment and treatment

Concerns patients have include job and scholastic performance, ability to care for their family and to return to a normal lifestyle. The mild cognitive impairments associated with the side effects of chemotherapy treatment usually subside within a year following the completion of treatment. Patients who are returning to work or school naturally wonder about the best timelines to do so. An assessment of their cognitive functioning can help with establishing when to return to the workplace or the classroom, and can also identify specific cognitive changes they are experiencing.

The role of a neuropsychologist includes assessing the cognitive function of a patient as compared to normative standards. Neuropsychologists also assess a patient’s ability to return to normal daily functioning and identify other issues that can affect cognition, such as fatigue, sleep problems, and depression and anxiety.

Elements of a neuropsychological evaluation include:

  • Patient history
  • A battery of tests of cognitive areas often affected by cancer treatment
  • Brief evaluation of psychological function and fatigue symptoms

The assessment can show the typical pattern of cognitive dysfunction associated with cancer treatment and rule out primary mood disorders or dementia.

To help mitigate cognitive issues, patients can adopt a number of compensatory strategies, including:

  • Using a planner or calendar for appointments, events, tasks, etc.
  • Making lists before going to the store
  • Using cell phone alarms as reminders
  • Staying organized and putting things away
  • Performing tasks in a serial fashion
  • Allowing extra time to complete tasks


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